Discovery of<i>N</i>-[(2<i>S</i>)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1<i>H</i>-inden-2-yl]-2-propanesulfonamide, a Novel Clinical AMPA Receptor Positive Modulator

Abstract

A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.